Tocilizumab is Associated with Increased Risk of Fungal Infections Among Critically Ill Patients with COVID-19 and Acute Renal Failure: An Observational Cohort Study.
Abstract Research QuestionDoes treatment with tocilizumab increase the risk of a fungal infection in critically ill patients with coronavirus-19?BackgroundNumerous therapies have been re-evaluated as possible treatment options for coronavirus-2019 caused by severe acute respiratory syndrome coronavirus-2. Tocilizumab is a humanized monoclonal antibody directed against the interleukin-6 receptor that has been proposed as a therapy for patients with severe coronavirus-19 pneumonia. The immunomodulatory effects of tocilizumab may have the unintended consequence of predisposing recipients to secondary infections. We sought to assess the risk of invasive fungal disease and the therapeutic impact of tocilizumab on hospital length of stay, duration of mechanical ventilation, and intensive care unit length of stay in critically ill patients with severe coronavirus-19.MethodsRecords of critically ill patients with coronavirus-2019 admitted from March to September 2020 at our institution were reviewed. The risk for fungal infections, intensive care unit length of stay, hospital length of stay, and duration of mechanical ventilation in those that received tocilizumab in addition to standard coronavirus-2019 treatments was assessed. ResultsFifty-six critically ill patients treated with dexamethasone and remdesivir for coronavirus-2019 were included, of which 16 patients also received tocilizumab. The majority of the cohort was African American, Asian, or other ethnic minorities (53.6%). Invasive fungal infections occurred in 10.7% of all patients and infection rates were significantly higher in the tocilizumab group than in the control group (31.2% vs 2.5%, Risk Difference [RD]= 28.8%, p<0.01). The increased risk in the tocilizumab group was strongly associated with renal replacement therapy. There was a dose-response relation between the risk of fungal infection and doses of tocilizumab, with 2.5% of infections occurring with zero doses, 20% with a single dose (RD=17.5%), and 50% with two doses (RD=47.5%) (trend test p<0.001). In addition, ICU LOS (23.4 days v 9.0 days, p <0.01), duration of mechanical ventilation (18.9 v. 3.5 days, p=0.01), and hospital LOS (29.1 v. 15.5, p <0.01) were increased in patients that received tocilizumab. ConclusionsRepurposed therapies, such as tocilizumab, may have a role in the treatment of severe coronavirus-2019 pneumonia but safety concerns remain. In this cohort, tocilizumab treatment was associated with an increased risk of fungal infection in those that were critically ill and received renal replacement therapy. Tocilizumab was also associated with increased ICU and hospital LOS and duration of mechanical ventilation.